Investigator:
Jessica Butts, PhD
Name of Institution:
William Marsh Rice University
Project Title:
Characterizing the Cellular Heterogeneity of the PPtg Using a Novel Marker – Spx
Investigator Bio:
Dr. Butts is an Assistant Professor in the Department of Bioengineering and a core faculty member of the Neuroengineering Initiative at Rice University in Houston, Texas. In 2024, she was named an Allen Institute Next Generation Leader. Her lab focuses on the intersection of developmental biology and tissue engineering to understand how the brainstem develops and functions.
Dr. Butts earned her B.S. in Biomedical Engineering from Washington University in St. Louis in 2013, and her Ph.D. in Bioengineering as an NSF GRFP Fellow from the University of California – San Francisco and Berkeley in 2017. During her undergraduate and graduate studies, she developed the first directed differentiation protocol for V2a interneurons—excitatory neurons found in the brainstem and spinal cord—from mouse and human embryonic stem cells. She then completed her postdoctoral training as an NIH NRSA Fellow at Baylor College of Medicine, where she researched neuronal fate decisions in the developing brainstem.
Her lab is now focused on understanding the role of the brainstem in central nervous system function and disease.
Objectives/Background:
While much of the research on Parkinson’s disease (PD) has focused on the basal ganglia, other brain regions, such as a small area deep in the brainstem called the pedunculopontine tegmental nucleus (PPTg) involved in alertness, movement and memory, are also affected. The goal of this project is to use a newly discovered marker, Spexin (Spx), to better define the neurons within the PPTg and understand how they connect to other brain regions, with the long-term goal of improving PD therapeutics.
Methods/Design:
This study will use a newly developed mouse model to identify and characterize neurons in the PPTg. Our mouse model highlights the cells that produce Spx, the new marker we identified for the PPTg. First, we will create a detailed map showing the different kinds of brain cells in the mouse PPTg. We will also look at existing data about how genes are switched on in the human brainstem to understand the composition of the human PPTg. Then, we will use our new mouse model to determine where the neurons in the PPTg project to in the brain. We will use a technique called light sheet microscopy as an advanced imaging technique that lets us see the connections between brain cells in a whole mouse brain.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Our study will lay the groundwork for developing new and improved PD treatments. Deep brain stimulation (DBS) of the PPTg has been used to treat PD symptoms, but with mixed success because we don’t fully understand the types of cells and their interplay in the PPTg. This project will define which brain cells in this area are important for PD symptoms, which could lead to more precise and effective targeting for DBS. Additionally, this study could reveal whether Spx plays a role in controlling both movement and non-movement symptoms in PD.